Detailed analysis by in vivo and in vitro methods of antitumor drug effects on hematopoietic precursor cells will be continued with emphasis on 2 problems: 1) A re-assessment of the possible specific cytotoxic effects of Myleran on murine pluripotential stem cells and of Actinomycin D on erythropoietin-responsive cells. A specific drug action is here defined as one not explainable on the basis of a particularly favorable combination of the cell-type's cycling characteristics and the cycle- or phase-specific action of the drug. 2) Potentiation of cytotoxicity of drugs through cell-cycle manipulation by bacterial endotoxin or other agents. In view of their therapeutic use in leukemias, effects of killed Corynebacteria or leukocyte injections on cycling fraction of CFC or CFC will be determined by the in vivo 5-FU method. Information on the mechanism underlying the cycle-inducing action of endotoxin will be sought by several approaches including: a) assessment of changes in CFU or CFC cycling fraction resulting from a reduction in population density of marrow cells; and b) comparison of the effects of endotoxin and of androgen on CFC cycling fraction and proliferation rate in mice made neutropenic by BCNU administration.